Infections caused by methicillin resistant Staphylococcus aureus (MRSA) and related gram positive pathogens are a growing medical concern. Vancomycin, a glycopeptide antibiotic, is currently the agent of choice for combating these infections which are predominantly encountered in hospital settings. With the increased usage of Vancomycin, the emergence of resistant stains of staphylococci is inevitable, and the first confirmed report of vancomycin resistance in Staphylococcus epidermidis was disclosed at the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, La., 1996. Consequently, there is a dire need to develop new agents with an alternative mode of action.
The present invention relates to novel penem compounds in which the releaseable liphophilic aromatic side-chain, tethered to the penem nucleus via a methylene linker, necessary for anti-MRSA activity replaces the non-releaseable liphophilic side-chains found in 2-aryl and 2-benzothiazolylthio carbapenem compounds. The present invention replaces the common simple ether based found in EPO 416,953, substituted carbon atoms found in EPO 507,313, and substituted amines found in WO 9523149. The antibacterial compounds of the present invention thus comprise an important contribution to therapy for treating infections caused by these difficult to control pathogens. There is an increasing need for agents effective against such pathogens (MRSA/MRCNS) which are at the same time relatively free from undesirable side effects.